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@article{van:2015:10.1186/s13148-015-0104-2,
author = {van, veldhoven K and Polidoro, S and Baglietto, L and Severi, G and Sacerdote, C and Panico, S and Mattiello, A and Palli, D and Masala, G and Krogh, V and Agnoli, C and Tumino, R and Frasca, G and Flower, K and Curry, E and Orr, N and Tomczyk, K and Jones, M and Ashworth, A and Swerdlow, A and Chadeau, M and Lund, E and Garcia-Closas, M and Sandanger, T and Flanagan, JM and vineis, P},
doi = {10.1186/s13148-015-0104-2},
journal = {Clinical Epigenetics},
title = {Epigenome-wide association study reveals decreased average methylation levels years before breast cancer diagnosis},
url = {http://dx.doi.org/10.1186/s13148-015-0104-2},
volume = {7},
year = {2015}
}

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TY  - JOUR
AB  - Background. Interest in the potential of DNA methylation in peripheral blood as a biomarker of cancer risk is increasing. We aimed to assess whether epigenome-wide DNA methylation measured in peripheral blood samples obtained before onset of the disease is associated with increased risk of breast cancer.Methods. We report on three independent prospective nested case-control studies from the European Prospective Investigation into Cancer and Nutrition (EPIC-Italy, n=162 matched case-control pairs); the Norwegian Women and Cancer study (NOWAC, n=168 matched pairs); and the Breakthrough Generations Study (BGS, n=548 matched pairs). We used the Illumina 450k array to measure methylation in the EPIC and NOWAC cohorts. Whole genome bisulphite sequencing (WGBS) was performed on the BGS cohort using pooled DNA samples, combined to reach 50x-coverage across ~16 million CpG sites in the genome including 450k array CpG sites. Mean β values over all probes were calculated as a measurement for epigenome-wide methylation.Results. In EPIC we found that high epigenome-wide methylation was associated with lower risk of breast cancer (OR per 1SD=0.61, 95%CI 0.47–0.80; -0.2% average difference in epigenome-wide methylation for cases and controls). Specifically, this was observed in gene bodies (OR=0.51, 95%CI 0.38–0.69) but not in gene promoters (OR=0.92, 95%CI 0.64–1.32). The association was not replicated in NOWAC (OR=1.03 95%CI 0.81–1.30). The reasons for heterogeneity across studies are unclear. However, data from the BGS cohort was consistent with epigenome-wide hypomethylation in breast cancer cases across the overlapping 450k probe sites (difference in average epigenome-wide methylation in case and control DNA pools=-0.2%).Conclusions. We conclude that epigenome-wide hypomethylation of DNA from pre-diagnostic blood samples may be predictive of breast cancer risk and may thus be useful as a clinical biomarker.
AU  - van,veldhoven K
AU  - Polidoro,S
AU  - Baglietto,L
AU  - Severi,G
AU  - Sacerdote,C
AU  - Panico,S
AU  - Mattiello,A
AU  - Palli,D
AU  - Masala,G
AU  - Krogh,V
AU  - Agnoli,C
AU  - Tumino,R
AU  - Frasca,G
AU  - Flower,K
AU  - Curry,E
AU  - Orr,N
AU  - Tomczyk,K
AU  - Jones,M
AU  - Ashworth,A
AU  - Swerdlow,A
AU  - Chadeau,M
AU  - Lund,E
AU  - Garcia-Closas,M
AU  - Sandanger,T
AU  - Flanagan,JM
AU  - vineis,P
DO  - 10.1186/s13148-015-0104-2
PY  - 2015///
SN  - 1868-7083
TI  - Epigenome-wide association study reveals decreased average methylation levels years before breast cancer diagnosis
T2  - Clinical Epigenetics
UR  - http://dx.doi.org/10.1186/s13148-015-0104-2
UR  - http://hdl.handle.net/10044/1/24501
VL  - 7
ER  -

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